Neoplasms

All Conditions

Rare Diseases

Rhabdoid Tumor

Children affected by an ATRT at time of surgical resection

genome expression analyzes in single cells

analyzes in singles cells

Franck BOURDEAUT, MD

Nelly BRIAND, PhD

Kevin Beccaria, MD, PhD, Pr

The aim is to describe at the cellular level the heterogeneity of rhabdoid tumors, and identify how this diversity influences resistance to treatment.

Rhabdoid tumors are aggressive cancers of infancy. Although frequently chemosensitive at the very beginning, they very often show resistance, suggesting some intra-tumor diversity or plasticity. Moreover, morphological analysis of rhadoid tumors often reveal some variety in tumor cell shapes and immunohistochemical profiling. Altogether, this suggests some intra-tumor heterogeneity, that has been scarcely studied so far.

This project aims to describe the intra-tumor heterogeneity by single-cell sequencing approaches.

After surgical resection, fresh tumor samples will be dissected and analysed using the 10X Chromium technology. Briefly, cells will be grouped in clusters according to their gene expression signalling, and each cluster will be defined in comparison with all other ones. Differential analyses will allow identifying the main characteristic of each cell sub-population. Potential filiations between clusters will be analysed using classical algorithms. The study will be performed on 10 to 15 tumor samples.

Rhabdoid Tumors Cellular Architecture by Single-cell Analyses (InnovRT-2)

Hétérogénéité Des Tumeurs Rhabdoides : Approches en " Cellules Uniques " Pour Identifier Des Cibles thérapeutiques

Identification of cell clusters - mean expression (RPKM unit) of gene set signtaures in each bioinformatically defined cluster

Fraction/percentage of cell clusters defined by primary outcome that are specific to each tumor and those that are shared by several or all samples

Mean expression (RPKM unit) of targetable genes (defined by the existence of adequate pharmacological inhibitor) in each tumor sample and clusters

Conducting therapeutic biological functional tests

Institut Curie

Assistance Publique - Hôpitaux de Paris

Blood and Lymph Conditions

Immune System Diseases

Nervous System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Lymphoma

Glioblastoma

Glioma

Sarcoma

Hodgkin Disease

Brain Neoplasms

Osteosarcoma

Wilms Tumor

Medulloblastoma

Diffuse Intrinsic Pontine Glioma

Neuroblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Ependymoma

Rhabdomyosarcoma

Sarcoma, Synovial

Desmoplastic Small Round Cell Tumor

Gliosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Connective and Soft Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Lymphosarcoma

Soft Tissue Sarcoma

Hodgkin Lymphoma

Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Brain Tumor, Childhood

Synovial Sarcoma

Neuroepithelioma

Malignant Germ Cell Tumor

Gliomatosis Cerebri

IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose

CLR 131

Jarrod Longcor

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma

An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children, Adolescents, and Young Adults With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors

DLT will be assessed by physical examination, vital signs, and laboratory values

Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults

Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)

Assessment via 131-I/CLR 131 SPECT/CT scans

Time from first infusion of CLR 131 until progression or recurrence of disease

Time from first infusion of CLR 131 until death due to any reason

Assessment of dosimetry via whole body planar imaging

Cellectar Biosciences, Inc.

Patients \<18 years with an ATRT having frozen samples

Characterization of the proteomic and phosphoproteomic landscape using mass spectrometry

Mass spectrometry

Kevin Beccaria, MD, PhD

The investigators aim to explore the inter tumor heterogeneity by a proteomic approach of a wide series of rhabdoid tumors, from both intra and extra cranial origins.

Context: Rhaboid tumors (RT) are aggressive cancers of young infants, exposed to the toxicity of heavy treatments often ineffective, which justifies the need to identify new treatment strategies. These tumors are characterized by the biallelic alteration of SMARCB1 gene, encoding one of the subunits of the SWI/SNF complex, a chromatin remodeler. These mutations are the only ones found in these very stable cancers, which offers few therapeutic targets that can be identified by genomic techniques. They are morphologically undifferentiated and pluriphenotypic, suggesting the existence of a cellular diversity still poorly described. To advance on these questions, the investigators' laboratory has developed a model of genetically engineered mouse model spontaneously developing RT, biologically very similar to their human counterparts.

Objectives and methods: The investigators' project aims to describe the proteomic and phosphoproteomic signatures of these tumors, so far described at the genome and transcriptome level; an integration of these pangenomic / pan-proteomic studies will reveal the most relevant features to target. The investigators will fully characterize the proteomic and phosphoproteomic landscape using mass spectrometry on a cohort of clinically, radiologically and histopathologically annoted ATRT, for which methylome and RNAseq profiling will also be done. The investigators will describe the proteomic features of each molecularly defined subgroups, and aim to correlate RNAseq changes with proteomic features.

Patients will be included if they or their legal representative have given a consent to such a study, and if frozen material is stored at Necker Hospital.

Expected results: This analysis helps to identify how to articulate several innovative therapeutic approaches, taking into account both the diversity of the cells to be treated, and the real targets, proteins, to inhibit or restore.

Finding New Targets by Proteomic Approaches (InnovRT1)

Heterogeneity in Rhabdoid Tumors : Proteomic and Single-Cell Analyses to Identify New Therapeutic Targets

Sainte Anne hospital

Symptoms and General Pathology

Recurrence

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Analgesics

Lipid Regulating Agents

Etoposide

Cytarabine

Cyclophosphamide

Bevacizumab

Angiogenesis Inhibitors

Etoposide phosphate

Thalidomide

Celecoxib

Fenofibric acid

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Growth Inhibitors

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Anti-Bacterial Agents

Anticholesteremic Agents

Hypolipidemic Agents

10mg/kg, intravenous (iv), biweekly, 1 year

35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year

16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year

Andreas Peyrl, MD

Irene Slavc, MD

Rebecca Loret de Mola

Rebecca Loret De Mola, MD

Ashley Ratcliffe

Virginia Harrod, MD

Elisabeth Hulla-Gumbsch

Martin Benesch, MD

Yvonne Ennemoser, MSc

Roman Crazzolara, MD

Martina Winkler

Georg Ebetsberger, MD

Neil Jones, MD

Agnes Gamper, MD

Alexandra Martincekova, MD

Jaroslav Sterba, MD

Zdenek Pavelka, MD

Klara Hruba

David Sumerauer, MD

Karsten Nysom, MD

Pierre Leblond, MD

Ingrid Torsvik

Ingrid Torsvik, MD

Alvaro Lassaletta, MD, PhD

Karin Fritzson

Anna Schröder- Håkansson

Magnus Sabel, MD

Birgitta Lannering, Prof

Birgitta Hellström

Pernilla Augustsson

Irene Devenney, MD

Yvonne Håkansson

Simon Johansson

Helena Mörse, MD

Carina Rinaldo

Yvonne Copeland

Stefan Holm, MD

Marita Wikström-Larsson

Mattias Mattsson

Katarina Vallin

Anders Öberg, MD

Monika Chocholous, MD

Patients with relapsed medulloblastoma, ependymoma and ATRT have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities. Antiangiogenetic therapy has emerged as new treatment option in solid malignancies. The frequent, metronomic schedule targets both proliferating tumor cells and endothelial cells, and minimizes toxicity. In this study the investigators will evaluate the use of biweekly intravenous bevacizumab in combination with five oral drugs (thalidomide, celecoxib, fenofibrate, and alternating cycles of daily low-dose oral etoposide and cyclophosphamide), augmented with alternating courses of intrathecal etoposide and cytarabine. The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma and ATRT, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life. The primary objective of the MEMMAT trial is to evaluate the activity of this multidrug antiangiogenic approach in these heavily pretreated children and young adults. Additionally, progression-free survival (PFS), overall survival (OS), as well as feasibility and toxicity will be examined.

3 Strata (medulloblastoma - 40 patients; ependymoma - 30 patients; ATRT - 30 patients)

Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT

A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma and ATRT

Response rate (Complete remission, partial response, stable disease =\[CR+PR+SD\]/n) 6 months after start of antiangiogenic treatment

The percentage of patients in the study who are alive for a certain period of time (6, 12, 24, and 36 months) after start of treatment with an antiangiogenic multidrug-regime

The percentage of patients in the study who are alive with a non-progressive disease for a certain period of time (6, 12, 24, and 36 months) after start of treatment with an antiangiogenic multidrug-regime.

To evaluate and document toxicities from chronic administration of these drugs at the doses prescribed in this protocol in patients with recurrent or progressive medulloblastoma. These will be descriptive in nature.

To evaluate the feasibility of achieving the prescribed drug doses given the reduced bone marrow tolerance after multiple relapses.

Quality of Life (QoL) will be evaluated by a generic quality of life instrument for children (the KINDL®-questionnaire).

To evaluate the influence of tumor biology(histologic subgroups, metastatic stage, age at first diagnosis \[\<3 years, \>3 years\]), age at start of antiangiogenic therapy, sex, duration of remission prior to antiangiogenic therapy, number of recurrences.

To evaluate serum markers for in-vitro correlative studies of tumor response.

Medical University of Vienna

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rhabdoid Tumors Cellular Architecture by Single-cell Analyses (InnovRT-2)	NCT04987476	ATRT	analyzes in sin...	- 17 Years	Assistance Publique - Hôpitaux de Paris
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma	NCT03478462	Pediatric Solid... Pediatric Lymph... Pediatric Brain... DIPG Neuroblastoma Ewing Sarcoma Rhabdomyosarcom... Osteosarcoma	CLR 131	2 Years - 25 Years	Cellectar Biosciences, Inc.
Finding New Targets by Proteomic Approaches (InnovRT1)	NCT04868799	ATRT	Mass spectromet...	- 17 Years	Assistance Publique - Hôpitaux de Paris
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT	NCT01356290	Medulloblastoma... Ependymoma Recu... ATRT Recurrent	Bevacizumab Thalidomide Celecoxib Fenofibric acid Etoposide Cyclophosphamid... Etoposide phosp... Cytarabine	- 19 Years	Medical University of Vienna
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT	NCT01356290	Medulloblastoma... Ependymoma Recu... ATRT Recurrent	Bevacizumab Thalidomide Celecoxib Fenofibric acid Etoposide Cyclophosphamid... Etoposide phosp... Cytarabine	- 19 Years	Medical University of Vienna

Spots Global Cancer Trial Database for atrt

Every month we try and update this database with for atrt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for atrt

Every month we try and update this database with for atrt cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for atrt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.